Formulation of a prophylactic vaccine against Pseudomonas aeruginosa

总结 铜绿假单胞菌（Pseudomonasaeruginosa，Pa）是引起严重感染的重要条件致病菌 烧伤、严重创伤、肺炎患者和需要插管的危重患者，或 漂浮导管由于抗生素耐药性，清除Pa是困难的。约有32，600例多药病例 耐药（MDR）Pa每年在住院患者中有2700例死亡和7.57亿美元的患者护理费用。 此外，Pa是囊性纤维化（CF）患者肺部感染的主要原因，其中>70%的患者发生肺部感染。 人口被他们的青少年长期殖民。军事人员受到严重影响， MDR Pa在战斗中受伤同样重要的是，负面影响的最大风险因素 与MDR Pa感染相关的结局是高龄。60岁以后， MDR Pa感染导致的发病率和死亡率。因此，具有广泛保护性的Pa疫苗具有很大的市场 最多可接种三次疫苗，为所有人提供全面保护。亿万 每年将提供疫苗剂量，销售额接近50亿美元。虽然有Pa疫苗正在开发中， 没有一个获得许可。我们技术的目标是一种预防性疫苗， 无论血清型如何，Pa的定殖都是为了保护脆弱的患者，我们的目标是 成熟成虫，在生物膜形成和宿主适应之前。当第一阶段完成后， 我们将优化疫苗配方，并在小鼠和兔子模型中证明保护效力。

SUMMARY Pseudomonas aeruginosa (Pa) is an important opportunistic human pathogen that causes severe infections in patients with burns, severe wounds, pneumonia, and critically ill patients who require intubation or catheterization. Clearing Pa is difficult due to antibiotic resistance. There are ~32,600 cases of multi-drug resistant (MDR) Pa in hospitalized patients annually with 2700 deaths and $757 million in patient care costs. Additionally, Pa is the major cause of pulmonary infections in cystic fibrosis (CF) patients with >70% of this population being chronically colonized by their teens. Military personnel are gravely impacted by the occurrence of MDR Pa in combat-related injuries. Equally important is the fact that the biggest risk factor for negative outcomes associated with infection by MDR Pa is advanced age. After age 60, there is a significant increase in morbidity and mortality resulting from MDR Pa infection. Thus, a broadly protective Pa vaccine has large market potential with up to three vaccinations providing complete protection to all humans. Hundreds of millions of vaccine doses would be given annually, approaching ~$5B in sales. While there are Pa vaccines in development, none have been licensed. The goal of our technology is a prophylactic vaccine that prevents initial colonization by Pa, regardless of serotype, to protect vulnerable patients, which we are targeting as mature adults for this study, prior to biofilm formation and host adaptation. When Phase I is completed, we will have optimized the vaccine formulation and demonstrated protective efficacy in mice and rabbit models.